Knee osteoarthritis (OA) is a major cause of disability among Veterans and is the primary indication of knee replacement in the VA. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed medications for knee OA. Though short-term studies have demonstrated that NSAIDs are more effective than placebo and acetaminophen, there are no long-term data supporting their use. This is of concern, because long-term use of NSAIDs is associated with significant morbidity and mortality. Guidelines have been published to improve safe use of NSAIDs; however, adherence to these evidence-based recommendations is low in the VA. There is therefore an important need to determine if the long-term use of NSAIDs offers any incremental benefit over safer alternatives. This is especially true for Veterans, a population at high risk for NSAID-induced toxicity. Cognitive behavioral therapy (CBT) is an effective and safe treatment alternative for OA. This modality is becoming increasingly available in the VA for treatment of chronic pain as well as other chronic disorders such as depression, post-traumatic stress disorder and insomnia. CBT can be successfully administered over the telephone and thus stands to benefit Veterans living in more remote areas with limited access to hospital or community-based outpatient clinics. In this study, we propose to conduct a 2-phase randomized withdrawal trial (RWT). The trial will focus on recruiting Veterans with knee OA who have been using NSAIDs for at least 3 months. In the first phase of the study, 544 Veterans with knee OA will be randomized to continue NSAIDs or to placebo for 4 weeks. This double-blind phase will enable us to infer whether placebo is non-inferior to continued NSAID use. In the second phase, subjects in the NSAIDs group will continue NSAIDs and those on placebo will stop taking the placebo and participate in a 12-week CBT program. The second, single-blind, phase will allow us to infer whether CBT is non-inferior to NSAIDs. All study data will be collected over the telephone thus enabling Veterans who have difficulty arranging transportation to the VA to participate. We will test for between-group differences in knee pain measured using the well-validated Western Ontario and McMaster Universities Osteoarthritis Index (primary outcome) at 4 and 16 weeks. We will also test for between group differences in lower extremity disability, subjects' global impression of change and use of co- therapies (secondary outcomes). As recommended for non-inferiority trials, we will perform both an intent to treat and per protocol analysis. Lastly, we will estimate the potential cost-effectiveness of the CBT protocol compared with continued NSAID use. Though it would be ideal for subjects randomized to the active study drug to continue their current NSAID, having the VA pharmacy formulate multiple different active drugs and maintaining the blind is not possible. Therefore, we will include a 2-week run-in period where study subjects will replace their NSAID with meloxicam. Meloxicam was chosen as the study drug because it is the most commonly prescribed at our center and has a favorable safety profile compared to other NSAIDS. If successful, the trial will improve the quality of care delivered to Veterans with chronic knee pain due to OA. The proposed strategy is particularly appealing because it replaces the widespread use of NSAIDs with a safer alternative, enables delivery of care to Veterans with limited access, and is likely to be cost saving.